The stimulation of quiescent BALB/c-3T3 cells to initiate DNA synthesis is regulated by the synergistic actions of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and somatomedin C (SmC). Transformation of BALB/c-3T3 cells abrogates the requirement for PDGF and plasma-derived factors. The elucidation of the mechanisms whereby growth factors control the cell cycle may lead to an understanding of the transformation process. PDGF has been shown to induce the synthesis of several unique proteins. The role of these proteins in cell cycle control is being investigated. Cyclic AMP has been shown to potentiate the effect of PDGF on the initiation of DNA synthesis. Studies to determine how cyclic AMP effects the action of PDGF are being conducted. The synergistic interactions of PDGF, EGF, and SmC are being studied in BALB/c-3T3 cells. These same polypeptides are being used to study growth initiation in other fibroblastic cells in order to determine the specificity of growth factors in growth regulations.